Abstract:During fear learning, anticipation of an impending aversive stimulus increases defensive behaviors. Interestingly, omission of the aversive stimulus often produces another response around the time the event was expected. This omission response suggests that the subject detected a mismatch between what was predicted and what actually occurred, thereby providing an indirect measure of cognitive expectancy. Here, we used functional magnetic resonance imaging to investigate whether omission-related brain activity reflects fear expectancy during learning and generalization of conditioned fear. During conditioning, a face expressing a moderate amount of fear (conditioned stimulus, CS+) signaled delivery of an aversive shock unconditioned stimulus (US), whereas the same face with a neutral expression was unreinforced. In a subsequent generalization test, subjects were presented with faces expressing more or less fear intensity than the CS+. Psychophysiological results revealed an increase in the skin conductance response (SCR) during learning when the US was omitted. Omission-related SCRs were also observed during the generalization test following the offset of high- but not low-intensity face expressions. Neuroimaging results revealed omission-related neural activity during learning in the anterior cingulate cortex, parietal cortex, insula, and striatum. These same regions also showed omission-related responses during the generalization test following highly expressive fearful faces. Finally, regression analysis on omission responses during the generalization test revealed correlations in offset-related SCRs and neural activity in the dorsomedial prefrontal cortex and posterior parietal cortex. Thus, converging psychophysiological and neural activity upon omission of aversive stimulation provides a novel metric of US expectancy, even to generalized cues that had no prior history of reinforcement.